tbuckley/cabot-search huggingface dataset:
Outcomes with novel combinations in nonclear cell renal cell carcinoma (nccRCC): ORACLE study.
Authors: Deepak Kilari, Aniko Szabo, Pooja Ghatalia, Tracy L Rose, Huaying Dong, Nicole Weise, Tony Z. Zhuang, Abdurahman Alloghbi, Rohit K. Jain, Ajjai Shivaram Alva, Abhishek Tripathi, Arnab Basu, Nancy B. Davis, James Brundage, Hamid Emamekhoo, Yousef Zakharia, Vadim S Koshkin, Mehmet Asim Bilen, Elisabeth I. Heath, Rana R. McKay
Journal: Journal of Clinical Oncology (2022)

4545 Background: Despite recent advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of combination therapies (including IO-IO, IO-VEGF, VEGF-mTOR) in subtypes of advanced nccRCC is unknown. Methods: In this multicenter retrospective analysis, we evaluated the efficacy of combination systemic therapies in patients with nccRCC. Eligible patients included those with nccRCC as determined by local genitourinary pathology review and receipt of one of three combination regimens during any line treatment (IO-IO, IO-VEGF, mTOR-VEGF). The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints were progression- free survival (PFS), disease control rate (DCR), and overall survival (OS). Results: Among 128 included patients, median age was 57 years; 66% were male and 65% white. Histologies included papillary (37%), unclassified (33%), chromophobe (16%), translocation (9%), and other (5 %). Among all patients, 69% had prior nephrectomy; 80% were IMDC intermediate/poor risk; 20% had sarcomatoid and/or rhabdoid differentiation, 27% and 29% had liver and bone metastasis respectively and 63% received combination treatment as first line. Comparison of outcomes based on treatment regimen, line of treatment and subtype is shown in the table. Median PFS and OS were longer with IO/IO and IO/VEGF compared to VEGF/ mTOR at 8.5, 9.5 and 3.7 months and 24.4, 18.2 and 15.4 months respectively. Conclusions: Antitumor activity was observed with novel combinations in nccRCC in both frontline and later line setting. Optimal management of nccRCC remains an unmet need and prospective data is warranted to guide treatment selection for this population. [Table: see text]
IMMUTACE: A biomarker-orientated phase II, single-arm, open-label AIO study of transarterial chemoembolization (TACE) in combination with nivolumab performed for intermediate-stage hepatocellular carcinoma (HCC; AIO-HEP-0217)—Updated efficacy results.
Authors: Anna Saborowski, Dirk Waldschmidt, Jan Hinrichs, Thomas Jens Ettrich, Uwe Marc Martens, Ardian Mekolli, Enrico N De Toni, Thomas Berg, Michael Geißler, Guido Hausner, Martin Maenz, Ursula Ehmer, Marta Kirstein, Arndt Vogel
Journal: Journal of Clinical Oncology (2022)

4116 Background: Immunotherapy based combinations recently revolutionized the treatment of patients (pts) with advanced HCC, but its significance in earlier stages remains to be determined. TACE is commonly used as first line treatment in intermediate HCC, but outcome of patients treated with TACE in real-life cohorts is still poor with a median overall survival (OS) below 20 months. The aim of this study was to determine the safety and efficacy of TACE combined with nivolumab. Methods: This is a phase II trial, that recruited 59 patients at 10 sites in Germany between 06/2018 and 06/2020. Pts received up to two TACE treatments followed by nivolumab (240 mg/ Q2W), initiated on day 2-3 after the first TACE session and continued until progression for a maximum treatment duration of two years. Primary endpoint was ORR (mRECIST; with ORR exceeding 55% (power = 80%; actual beta 0.17) as promising for further investigations). Secondary endpoints include mPFS, mTTFS (median time to failure of strategy), mOS, QoL, and safety/tolerability. Tumor tissue was obtained at baseline and blood samples were collected longitudinally for translational research. Results: 49 pts (14.3% HCV and 8.2% HBV) were enrolled and received at least one dose of nivolumab, median tumor size was 4.5 cm (0.9 – 15 cm) and median number 3 (1 – 12). ORR by mRECIST was 71.4% (CR: 16.3%, PR: 55.1%, SD 4.1%, PD: 14.3%). At a median follow-up of 20 months, mPFS was 7.2 mo (95% CI; 5.3 – 11.2; 40 events), mTTFS was 11.2 mo (95% CI; 7.2, 13.5; 42 events) and mTTSST (median time to subsequent systemic therapy) was 24.9 mo (95% CI; 12.2, - ; 21 events). Median duration of Nivolumab was 8.3 months and mOS was 28.3 mo (95% CI; 20 – not estimable; 23 events). Grade ≥3 treatment-related adverse events occurred in 34.7% of patients. Correlative analysis of efficacy with genetic alterations, gene expression signatures and changes of immune cell populations will be reported soon. Conclusions: The study met its primary endpoint and provides evidence for the efficacy of TACE in combination with nivolumab without new safety signals in pts with intermediate HCC and no prior systemic therapy. Our findings support further evaluation of nivolumab-based combinations for the treatment of intermediate HCC. Disclaimer: This study was supported with drug and funding by Bristol-Myers-Squibb. Clinical trial information: NCT03572582.
Implementation of universal, pan-cancer germline genetic testing in patients with cancer in Jordan.
Authors: Hikmat Abdel-Razeq, Abdelghani Tbakhi, Ramiz Abuhijlih, Lama Abujamous, Mahmoud Al Masri, Razan Abukhashabeh, Asia Mitchell, Brandie Heald, Sarah M. Nielsen, Robert Luke Nussbaum, Edward D. Esplin
Journal: Journal of Clinical Oncology (2022)

10580 Background: Detection of pathogenic germline variants (PGVs) has a significant and growing impact on the management of patients with many types of cancer. Most research to date evaluated individuals of European background, which can result in skewed genetic testing criteria and variant interpretation. Additional data are needed from diverse populations. This study aimed to investigate a universal germline testing strategy and the pattern and frequency of PGVs among all newly diagnosed cancer patients at a single center in Jordan. Methods: In this prospective, observational study, consecutive patients newly diagnosed with cancer were classified as meeting or not meeting National Comprehensive Cancer Network (NCCN) germline genetic testing criteria. All patients underwent an 84-gene panel test, independent of age, stage or family history. Demographics and clinical history were collected and analyzed from information provided by the clinicians on the test requisition form. Descriptive statistics were employed, and statistical significance was determined by two-tailed Fisher’s exact test and unpaired t test. Results: In total, 1377 cancer patients of Arabic background were enrolled, of which 831 (60.3%) met NCCN criteria (Table). PGVs were identified in 210 (15.3%). Excluding the 29 patients who were carriers for autosomal recessive conditions, 192 PGVs were identified in 181 (13.1%) patients. PGVs were most commonly identified in APC (p.I1307K variant, 55, 28.6%), BRCA2 (35, 18.2%), BRCA1 (21, 10.9%), and TP53 (12, 6.3%). While patients who met NCCN testing criteria were more likely to have a PGV (p&lt;0.0001), 44 (24.30%) patients with PGVs did not meet criteria. Among those with PGVs, 177 (97.8%) were potentially eligible for increased screening per NCCN/expert opinion guidelines, 69 (38.1%) targeted therapies, and 89 (49.2%) clinical trials; this included 41 (22.7%), 6 (3.3%), and 14 (7.7%) patients, respectively, that did not meet NCCN testing criteria. 1445 variants of uncertain significance (VUS) were identified in 833 (57.7%) patients, but no difference in VUS rate was observed between those meeting and not meeting criteria (p=0.7354). Conclusions: Overall PGV rate among cancer patients from one center in Jordan was similar to that reported in the literature. While the VUS rate was high, similar rates were observed in those meeting and not meeting criteria. Testing restricted to guidelines could have missed approximately a quarter of patients with PGVs, &gt;95% of whom might qualify for increased screening, targeted therapies, and/or clinical trials. [Table: see text]
A prognostic model for overall survival in primary central nervous system lymphoma using post-steroid neutrophil-lymphocyte ratio.
Authors: Yu Tung Lo, Vivian Yujing Lim, Melissa Ng, Ya Hwee Tan, Jianbang Chiang, Esther Wei Yin Chang, Jason Chan, Eileen Yi Ling Poon, Nagavalli Somasundaram, Mohamad Farid Rin Harunal Rashid, Miriam Tao, Lim Soon Thye, Valerie Shiwen Yang
Journal: Journal of Clinical Oncology (2022)

e14049 Background: Ratios of differential blood counts (hematological indices, HI) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSL), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HI could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HI were calculated at three time-points: baseline (pre-steroid), pre-chemoimmunotherapy (post-steroid) and post-chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan-Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan-Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR≥4.0, HR 0.42, 95% CI: 0.21-0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR≥241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03) respectively only. Decision-tree model using age ≤70, post-steroid NLR &gt; 4.0, and pre-steroid (baseline) NLR &lt; 2.5 divided patients into three risk categories – low, medium, high – and achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusions: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed accurate and well-calibrated stratification into three risk groups.
Outcomes of classic Hodgkin lymphoma, relapsed within one year of diagnosis, in the era of novel agents.
Authors: Sanjal Desai, Michael Alexander Spinner, Kevin A. David, Veronika Bachanova, Gaurav Goyal, Raya Saba, Kathleen Anne Dorritie, Jacques Mario Azzi, Elyse Harris, Brendon Fusco, Nuttavut Sumransub, Haris Hatic, Uroosa Ibrahim, Siddharth Iyengar, Katherine Cynthia Rappazzo, Firas Baidoun, Victor Manuel Orellana-Noia, Catherine S. Magid Diefenbach, Ranjana H. Advani, Ivana N. M. Micallef
Journal: Journal of Clinical Oncology (2022)

7515 Background: Primary refractory disease (PRD) and early relapse (ER) are predictors of poor prognosis in classic Hodgkin lymphoma (cHL). In this multicenter retrospective study, we describe outcomes of PRD and ER in pts with relapsed/refractory (R/R) cHL treated with salvage therapy (ST) and autologous stem cell transplant (ASCT). Methods: Of 14 sites, adult patients with R/R cHL who received ST and underwent ASCT were enrolled. PRD was defined as progression on frontline chemoimmunotherapy or within 6 months of diagnosis. ER was defined as relapse from 6 months-1 yr of diagnosis. Pts who relapsed &gt;1 yr of diagnosis were called late relapses (LR). Study objectives were Overall response rates (ORR), CR rates, PFS, and OS. Results: Of 986 total pts, 160 had PRD, 365 had ER and 461 had LR. Significantly higher number of pts with PRD, but not ER, had bulky disease (41% vs 27%, p&lt;0.01) and B symptoms (53% vs 38%, p&lt;0.001) than LR. Higher proportions of pts with PRD and ER required &gt;1 line of ST (44% vs 30% vs 23%, p&lt;0.001) before ASCT and received BV maintenance (25% vs 24% vs 16%, p&lt;0.05). When adjusted for B symptoms and Bulky disease, PRD and ER had significantly lower ORR (65% vs 76% vs 84%, p&lt;0.001) and CR (37% vs 46% vs 57%, p&lt;0.001) to first ST than LR. Pts with PRD and ER had significantly lower PFS (56.3%, 61.4%, vs 77.6%, p&lt;.0001) and OS (93% vs 89% vs 94%, p=0.01) than LR. In pts with ER, Brentuximab/bendamustine (BBV) and brentuximab vedotin/nivolumab (BV/nivo) had a trend towards higher ORR (92% vs 92% vs 75%) but significantly higher CR (79.2% vs 76% vs 42%, p&lt;0.01) than platinum based chemotherapy (PBC). In pts with PRD, BBV and BV/Nivo had a statistically insignificant trend towards higher ORR and CR than PBC. The table shows 2 yr PFS by type of ST in PRD, ER, LR. There was no difference in PFS by time to relapse in BV/nivo, CPI and miscellaneous agents. BV/Nivo had a significantly higher PFS than PBC in PRD (88% vs 48%, p&lt;0.05) and ER (95% vs 57%, p&lt;0.05). There was no difference in PFS of PBC and other ST in PRD, ER or LR. OS was not significantly associated with type of ST in either group. Conclusions: PRD and ER are associated with lower response to ST and survival after ASCT compared to late relapse. In pts with PRD and ER, BV/Nivo has high ORR and CR and leads to significantly higher PFS comparable to pts with late relapse and may be preferable ST regardless of time to relapse. [Table: see text]
“More than conquerors”: A qualitative analysis of war metaphors for patients with cancer.
Authors: Monica Himaani Bodd, Nikki C. Daniels, Hermioni L. Amonoo, Tyler P. Tate, Kris W. Herring, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2022)

e24134 Background: Limited research suggests that war metaphors may be harmful for patients with cancer. For instance, it has been claimed that the use of war metaphors is associated with increased anxiety and depression, as well as poor coping for patients with cancer. However, little is known about how patients use and perceive these metaphors. Metaphors, which are intrinsic to the human conceptual system, help articulate patients’ experiences and needs. In this study, we explored patient narratives of illness metaphors in cancer, focusing particularly on war metaphors. Methods: Fifteen patients diagnosed with various stages of lung, colorectal or breast cancer completed semi-structured qualitative interviews about their use of metaphors after their cancer diagnoses. Interviews explored war metaphors in the context of treatment decisions, aggressiveness of care, and quality of life. Patients were also provided with a curated list of metaphors and asked about their use and experience thereof. Transcribed interviews were organized and analyzed by descriptive content analysis using NVivo software. Results: The most used metaphor categories were: 1) nature (e.g., journey, season); 2) militaristic (e.g., battle, victory, fight); and 3) uncertainty (e.g., mystery, puzzle). War metaphors were frequently referenced in patients’ support communities rather than in hospital or clinician encounters. Next, all patients with non-metastatic disease (n = 7) used war metaphors to describe their illness experience. Among all patients who used metaphorical language to describe their experience (n = 14), the only ones who did not use war metaphors (n = 2) had metastatic disease; these patients found war metaphors to be unhelpful due to their sense of having no control over the outcome. Lastly, participants reported that war metaphors served the following purposes in their illness experience with cancer: 1) promoted perseverance in the face of adversity, 2) expressed optimism, and 3) allowed them to relate cancer to previous life challenges. Conclusions: The hypothesis that war metaphors are invariably counterproductive for patients appears to be misguided. Metaphors of fighting, victory and battle worked both to empower and harm patients in this study, depending on the individual patient and their prognosis. While more prospective studies with robust sample sizes are needed to elucidate the role of metaphors in the lived experience of patients with cancer, our patients suggest the need to individualize, acknowledge and explore these metaphors for cancer populations.
Efficacy and safety study of fotemustine and bevacizumab in patients with recurrent glioblastoma.
Authors: Laura Sánchez Escudero, María Amor Urbano, María Yeray Rodríguez Garcés, Fátima Toscano Murillo
Journal: Journal of Clinical Oncology (2022)

e14041 Background: Glioblastoma (GBM) is highly vascularized tumor with elevated expression of vascular endothelial growth factor (VEGF). Bevacizumab (Bz) is a humanized monoclonal antibody against VEGF, which alone or associated with chemotherapy has obtained optimal results. However, the most suitable combination with bevacizumab is yet unknown. The objective of our study is to evaluate the efficacy and safety of Bz and fotemustine (Ft) in patients (pts) with recurrent GBM of the Huelva area and to compare our results with those published in the phase II study of the Italian Association of Neuro-oncology (AINO). Methods: Observational and descriptive study of the combination of Ft-Bz in GBM at first relapse after standard radiotherapy and TMZ concomitant in the hospital area of Huelva during the years 2010-2021. We used the same therapeutic scheme of the phase II study of AINO and the IBM SPSS Statistics 22 program to analyze the variables. Results: 42 pts were treated, 16 women and 25 men. Median age 52 years. ECOG 0-1 in 85.4%. 65.9% and 92.7% received antiepileptics and corticosteroids, respectively. In 90.2%, methylation status of the promoter of O 6 -methylguanine-DNA methyltransferase (MGMT) was not evaluated. Previously, 56.1% of the pts underwent total/subtotal resection, 29.3% partial and 14.6% were not resected, followed by concomitant radiotherapy and temozolamide in 100% of cases. 35.7% relapsed in less than 3 months after adjuvant treatment. 61% presented unifocal relapse and 39% multifocal. 46.3% of the pts had stable disease, 24.4% partial response and 2.4% complete response. 22% presented grade 3-4 toxicity. The most frequent toxicities are listed in the table. The median progression-free survival (PFS) was 6 months (95% CI 4.18-7.82) and the median overall survival (OS) was 7 months (95% CI 4.22-9.77). Conclusions: The results obtained in our study were similar to those of other previously published studies of Bz in combination with Ft. Although PFS was slightly higher than the phase II study AINO, OS was lower, probably due to the inclusion of a high rate of rapid progressors pts. Treatment tolerance was similar to that in the phase II study AINO. An increase in hematologic adverse events stands out in our pts. Therefore, this scheme can be a valid alternative in the management of recurrent GBM.[Table: see text]
Comprehensive analysis of non-transplant central nervous system lymphoproliferative disease associated with immunosuppressant use.
Authors: Ramya Tadipatri, Chukwuyem Ekhator, Ram Narayan, Amir Azadi, Kevin C.J. Yuen, Jai Grewal, Ekokobe Fonkem
Journal: Journal of Clinical Oncology (2022)

e14043 Background: Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens, with additional survival benefit gained by CD-20 targeting with rituximab. With increasing prevalence of autoimmune disease and a corresponding rapid rate of development and approval of new immunosuppressant medications, a new type of lymphoproliferative disorder (LPD) has been described, known as iatrogenic immunodeficiency associated LPD. These disorders are typically EBV positive and have distinct histologic and genetic features. Furthermore, many of them arise in the setting of prior methotrexate use, raising the question of whether standard HD-MTX based regimens would still be effective. Our objective was to further characterize this disorder, with a focus on cases with central nervous system involvement, and to determine the optimal management strategy. Methods: We describe a case of a 76-year-old female with iatrogenic immunodeficiency associated PCNSL following 10 years of mercaptopurine, which was successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency associated LPD involving the central nervous system (CNS). We used a linear probability statistical model to determine correlations with outcome. Results: While the majority of immunosuppressants were associated with EBV positive tumors, natalizumab was associated with EBV negative tumors (95% CI -0.951, -0.076), and EBV positive tumors were associated with improved outcomes (95% CI 0.074, 0.687). Surgical resection (95% CI 0.028, 0.574) was associated with improved outcomes, although limited by potential confounding effect. Although they did not reach statistical significance, antiviral treatment (95% CI -0.039, 0.459) and rituximab (95% CI -0.073, 0.524) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement. Conclusions: Based on this data, we propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency associated LPD of the CNS. However, further study through randomized clinical trials is warranted.